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NCT01982630

Study of the Safety and Efficacy of MK-8521 Compared to Placebo and a Diabetes Drug in Participants With Type 2 Diabetes Mellitus (MK-8521-003)

Completed Phase 1 Results posted Last updated 8 March 2022
What this trial tests

Phase 1 trial testing MK-8521 in Diabetes Mellitus in 87 participants. Completed in 3 October 2014.

Timeline
7 November 2013
Primary endpoint
3 October 2014
3 October 2014

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment87
Start date7 November 2013
Primary completion3 October 2014
Estimated completion3 October 2014

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 18 to 65, any sex, with Diabetes Mellitus. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Experiencing Adverse Events (AEs) in Part 1 Primary · Up to approximately 42 days

An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adver

GroupValue95% CI
Part 1: MK-8521 64 μg/Day5
Part 1: MK-8521 120 μg/Day5
Part 1: MK-8521 34 μg/Day1
Part 1: MK-8521 72 μg/Day4
Part 1: Liraglutide 0.6 mg/Day2
Part 1: Liraglutide 1.2 mg/Day7
Part 1: Liraglutide 1.8 mg/Day2
Part 1: Placebo for MK-85215
Number of Participants Experiencing Adverse Events (AEs) in Part 2 Primary · Up to approximately 57 days

An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adver

GroupValue95% CI
Part 2: MK-8521 64 μg/Day8
Part 2: MK-8521 120 μg/Day14
Part 2: MK-8521 180 μg/Day6
Part 2: MK-8521 240 μg/Day13
Part 2: MK-8521 300 μg/Day8
Part 2: Liraglutide 0.6 mg/Day8
Part 2: Liraglutide 1.2 mg/Day8
Part 2: Liraglutide 1.8 mg/Day12
Part 2: Placebo for MK-8521-T2DM3
Part 2: MK-8521 64 µg/Day-Non-Diabetic Overweight/Obese2
Part 2: MK-8521 120 µg/Day-Non-Diabetic Overweight/Obese4
Number of Participants Discontinuing Study Drug Due to Adverse Events (AEs) in Part 1 Primary · Up to approximately 14 days

An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adver

GroupValue95% CI
Part 1: MK-8521 64 μg/Day2
Part 1: MK-8521 120 μg/Day0
Part 1: MK-8521 34 μg/Day0
Part 1: MK-8521 72 μg/Day0
Part 1: Liraglutide 0.6 mg/Day1
Part 1: Liraglutide 1.2 mg/Day0
Part 1: Liraglutide 1.8 mg/Day0
Part 1: Placebo for MK-85210
Number of Participants Discontinuing Study Drug Due to Adverse Events (AEs) in Part 2 Primary · Up to approximately 29 days

An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adver

GroupValue95% CI
Part 2: MK-8521 64 μg/Day0
Part 2: MK-8521 120 μg/Day0
Part 2: MK-8521 180 μg/Day0
Part 2: MK-8521 240 μg/Day1
Part 2: MK-8521 300 μg/Day0
Part 2: Liraglutide 0.6 mg/Day0
Part 2: Liraglutide 1.2 mg/Day1
Part 2: Liraglutide 1.8 mg/Day1
Part 2: Placebo for MK-8521-T2DM1
Part 2: MK-8521 64 µg/Day-Non-Diabetic Overweight/Obese0
Part 2: MK-8521 120 µg/Day-Non-Diabetic Overweight/Obese0
Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 7 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 Primary · Baseline (predose Day 1) and up to 24 hours post Day 7 dose

Semi-recumbent heart rate was assessed at baseline on Day 1; Day 7 at predose, 2, 4, 6, 8, 12, 13, 14, 15, 16, 22 hours postdose; and prior to dosing on Day 8. Heart rate was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr was calculated as the area under the measurement-time curve (AUC) divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 7 minus baseline where b

GroupValue95% CI
Part 1: MK-8521 64/120 μg/Day7.193.48 – 10.89
Part 1: MK-8521 34/72 μg/Day1.17-2.21 – 4.55
Part 1: Liraglutide 0.6/1.2/1.8 mg/Day7.423.74 – 11.09
Part 1: Placebo for MK-85215.692.39 – 8.99
Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 7 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 Primary · Baseline (predose Day 1) and up to 24 hours post Day 7 dose

Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 7: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 8. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 7 minus baseline where baseline was defined as predose on Day 1.

GroupValue95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM1.990.10 – 3.88
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM4.101.87 – 6.34
Part 2: Placebo for MK-8521-T2DM-0.54-3.80 – 2.73
Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 14 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 Primary · Baseline (predose Day 1) and up to 24 hours post Day 14 dose

Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 14: predose, 2, 4, 6, 8, 12, 13, 14, 15, 16, 22 hours postdose and prior to dosing on Day 15. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 14 minus baseline where baseline was defined as predose on Day 1.

GroupValue95% CI
Part 1: MK-8521 64/120 μg/Day9.675.97 – 13.37
Part 1: MK-8521 34/72 μg/Day3.900.52 – 7.28
Part 1: Liraglutide 0.6/1.2/1.8 mg/Day10.326.65 – 14.00
Part 1: Placebo for MK-85219.816.51 – 13.12
Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 14 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 Primary · Baseline (predose Day 1) and up to 24 hours post Day 14 dose

Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 14: predose, 2, 4, 6, 8, 12, 16, hours postdose; and prior to dosing on Day 15. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 14 minus baseline where baseline was defined as predose on Day 1.

GroupValue95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM5.052.79 – 7.30
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM5.933.27 – 8.60
Part 2: Placebo for MK-8521-T2DM-0.20-4.32 – 3.93
Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 19 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 Primary · Baseline (predose Day 1) and up to 24 hours post Day 19 dose

Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 19: predose, 2, 4, 6, 8, 12, 16, hours post dose; and prior to dosing on Day 20. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 19 minus baseline where baseline was defined as predose on Day 1.

GroupValue95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM5.623.19 – 8.05
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM6.203.32 – 9.07
Part 2: Placebo for MK-8521-T2DM-2.14-6.66 – 2.37
Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 24 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 Primary · Baseline (predose Day 1) and up to 24 hours post Day 24 dose

Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 24: predose, 2, 4, 6, 8, 12, 16, hours postdose; and prior to dosing on Day 25. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 24 minus baseline where baseline was defined as predose on Day 1.

GroupValue95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM7.304.43 – 10.17
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM5.952.50 – 9.41
Part 2: Placebo for MK-8521-T2DM-0.99-6.28 – 4.29
Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 29 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 Primary · Baseline (predose Day 1) and up to 24 hours post Day 29 dose

Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; and Day 29: predose, 2, 4, 6, 8, 12, 16 and 24 hours postdose. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 29 minus baseline where baseline was defined as predose on Day 1.

GroupValue95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM8.305.31 – 11.29
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM5.842.26 – 9.43
Part 2: Placebo for MK-8521-T2DM-1.31-6.81 – 4.19
Change From Baseline in Peak Heart Rate (PHR) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 Primary · Baseline (predose Day 1) and up to 24 hours post Day 7 dose

PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 7: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 8. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 7 minus baseline where baseline was defined as predose on Day 1.

GroupValue95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM7.945.76 – 10.13
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM11.919.30 – 14.53
Part 2: Placebo for MK-8521-T2DM8.654.86 – 12.43

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 42 days for Part 1 and up to approximately 57 days for Part 2. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part 1: MK-8521 64 μg/Day
Serious: 1/9 (11%)
Deaths: 0/10
Part 1: MK-8521 120 μg/Day
Serious: 0/7 (0%)
Deaths: 0/7
Part 1: MK-8521 34 μg/Day
Serious: 0/8 (0%)
Deaths: 0/8
Part 1: MK-8521 72 μg/Day
Serious: 0/8 (0%)
Deaths: 0/8
Part 1: Liraglutide 0.6 mg/Day
Serious: 0/11 (0%)
Deaths: 0/11
Part 1: Liraglutide 1.2 mg/Day
Serious: 0/11 (0%)
Deaths: 0/11
Part 1: Liraglutide 1.8 mg/Day
Serious: 0/8 (0%)
Deaths: 0/8
Part 1: Placebo for MK-8521
Serious: 0/8 (0%)
Deaths: 0/8
Part 2: MK-8521 64 μg/Day T2DM
Serious: 0/18 (0%)
Deaths: 0/18
Part 2: MK-8521 120 μg/Day T2DM
Serious: 0/18 (0%)
Deaths: 0/18
Part 2: MK-8521 180 μg/Day T2DM
Serious: 0/18 (0%)
Deaths: 0/18
Part 2: MK-8521 240 μg/Day T2DM
Serious: 1/18 (6%)
Deaths: 0/18
Part 2: MK-8521 300 μg/Day T2DM
Serious: 0/15 (0%)
Deaths: 0/15
Part 2: Liraglutide 0.6 mg/Day T2DM
Serious: 0/14 (0%)
Deaths: 0/14
Part 2: Liraglutide 1.2 mg/Day T2DM
Serious: 0/13 (0%)
Deaths: 0/13
Part 2: Liraglutide 1.8 mg/Day T2DM
Serious: 0/13 (0%)
Deaths: 0/13
Part 2: Placebo for MK-8521-T2DM
Serious: 0/6 (0%)
Deaths: 0/6
Part 2: MK-8521 64 μg/Day-Non-Diabetic Overweight/Obese
Serious: 0/8 (0%)
Deaths: 0/8
Part 2: MK-8521 120 μg/Day-Non-Diabetic Overweight/Obese
Serious: 0/8 (0%)
Deaths: 0/8

Serious adverse events (4 terms)

ReactionSystemPart 1: MK-8521 64 μg/DayPart 1: MK-8521 120 μg/DayPart 1: MK-8521 34 μg/DayPart 1: MK-8521 72 μg/DayPart 1: Liraglutide 0.6 mg…Part 1: Liraglutide 1.2 mg…Part 1: Liraglutide 1.8 mg…Part 1: Placebo for MK-8521Part 2: MK-8521 64 μg/Day …Part 2: MK-8521 120 μg/Day…Part 2: MK-8521 180 μg/Day…Part 2: MK-8521 240 μg/Day…Part 2: MK-8521 300 μg/Day…Part 2: Liraglutide 0.6 mg…Part 2: Liraglutide 1.2 mg…Part 2: Liraglutide 1.8 mg…Part 2: Placebo for MK-852…Part 2: MK-8521 64 μg/Day-…Part 2: MK-8521 120 μg/Day…
Sick sinus syndromeCardiac disorders
Supraventricular tachycardiaCardiac disorders
ConvulsionNervous system disorders
PresyncopeNervous system disorders
Other adverse events (108 terms — click to expand)

ReactionSystemPart 1: MK-8521 64 μg/DayPart 1: MK-8521 120 μg/DayPart 1: MK-8521 34 μg/DayPart 1: MK-8521 72 μg/DayPart 1: Liraglutide 0.6 mg…Part 1: Liraglutide 1.2 mg…Part 1: Liraglutide 1.8 mg…Part 1: Placebo for MK-8521Part 2: MK-8521 64 μg/Day …Part 2: MK-8521 120 μg/Day…Part 2: MK-8521 180 μg/Day…Part 2: MK-8521 240 μg/Day…Part 2: MK-8521 300 μg/Day…Part 2: Liraglutide 0.6 mg…Part 2: Liraglutide 1.2 mg…Part 2: Liraglutide 1.8 mg…Part 2: Placebo for MK-852…Part 2: MK-8521 64 μg/Day-…Part 2: MK-8521 120 μg/Day…
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
ConstipationGastrointestinal disorders
Lipase increasedInvestigations
HeadacheNervous system disorders
Abdominal pain upperGastrointestinal disorders
DyspepsiaGastrointestinal disorders
TachycardiaCardiac disorders
Ear painEar and labyrinth disorders
Abdominal painGastrointestinal disorders
VomitingGastrointestinal disorders
Skin abrasionInjury, poisoning and procedural complications
Decreased appetiteMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
PruritusSkin and subcutaneous tissue disorders
PalpitationsCardiac disorders
Sinus tachycardiaCardiac disorders
Supraventricular tachycardiaCardiac disorders
Tachycardia paroxysmalCardiac disorders
Ventricular extrasystolesCardiac disorders
Ventricular tachycardiaCardiac disorders
Vision blurredEye disorders
Abdominal discomfortGastrointestinal disorders
Abdominal distensionGastrointestinal disorders
Aphthous stomatitisGastrointestinal disorders
Change of bowel habitGastrointestinal disorders
Dry mouthGastrointestinal disorders
FlatulenceGastrointestinal disorders
Gingival painGastrointestinal disorders
HaematocheziaGastrointestinal disorders
HaemorrhoidsGastrointestinal disorders
Mouth ulcerationGastrointestinal disorders
RegurgitationGastrointestinal disorders
RetchingGastrointestinal disorders
ToothacheGastrointestinal disorders
Application site dermatitisGeneral disorders
Application site erythemaGeneral disorders
Application site irritationGeneral disorders
Application site pruritusGeneral disorders
AstheniaGeneral disorders

Most-reported serious reactions: Sick sinus syndrome, Supraventricular tachycardia, Convulsion, Presyncope.

Data from ClinicalTrials.gov NCT01982630 adverse events section.

Sponsor's own description

This study will evaluate the safety, efficacy, and pharmacokinetics of MK-8521 given once daily compared to placebo and another diabetes drug in participants with Type 2 diabetes mellitus (T2DM). This study was modified by a protocol amendment to a 2-part trial to further test the safety and tolerability of MK-8521 at higher doses and to compare MK-8521 pharmacokinetics between participants with T2DM and healthy participants. An additional cohort of T2DM participants and a cohort of non-diabetic obese participants has been added.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Beyond Glucagon-like Peptide-1: Is G-Protein Coupled Receptor Polypharmacology the Path Forward to Treating Metabolic Diseases?
    Sloop KW, Briere DA, Emmerson PJ, Willard FS. · · 2018 · cited 30× · PMID 32219200 · DOI 10.1021/acsptsci.8b00009

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Other trials of MK-8521

Trials testing the same drug.

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Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing